Key result
Childhood ALL survivors show no significant increase in cardiac autonomic dysfunction vs controls.
Why the study?
Cardiac autonomic dysfunction is possible after treatment for childhood cancer, but its prevalence, functional impact, and treatment-related risk factors in adult survivors of childhood acute lymphoblastic leukemia needed evaluation.
Does treatment for childhood acute lymphoblastic leukemia increase the prevalence of cardiac autonomic dysfunction and impair exercise response in adult survivors compared to matched controls?
Cross-Sectional (n=663)
No
Does treatment for childhood acute lymphoblastic leukemia increase the prevalence of cardiac autonomic dysfunction and impair exercise response in adult survivors compared to matched controls?
Over one-third of adult survivors of childhood ALL exhibit cardiac autonomic dysfunction—particularly those with obesity or prior exposure to cyclophosphamide with high-dose vincristine/corticosteroids—which is associated with reduced exercise tolerance and represents a modifiable target for exercise rehabilitation.
Similar CAD prevalence does not support routine screening; leaves open heart rate recovery as a marker of exercise intolerance in ALL survivors.
Background Cardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment‐related risk factors for CAD. Procedure Participants were treated for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital between 1980 and 2003 ( N = 338). A comparison group matched for race/ethnicity, age, and sex was also recruited ( N = 325). Resting heart rate (HR) was assessed via electrocardiogram, and heart rate recovery (HRR) and exercise capacity were evaluated with submaximal cardiopulmonary exercise testing. Results CAD was present in 33.7% of survivors and 27.6% of controls ( P = 0.09). Although mean resting HR did not differ between survivors and controls (74 ± 12 vs 72 ± 12 beats per minute (bpm), P = 0.07), survivors had lower mean HRR than controls (22 ± 9 vs 25 ± 10 bpm; P < 0.001). Survivors with CAD had lower peak exercise tolerance (25.7 ± 6.5 vs 21.2 ± 4.9 mL/kg/min, P < 0.001) than those without. Survivors treated with cyclophosphamide in combination with vincristine ≥38 mg/m 2 and/or glucocorticoids ≥10 000 mg/m 2 were 1.56 (95% CI 1.09‐2.24) times more likely to have CAD than those without this treatment. Obese survivors were 1.78 (95% CI: 1.31‐2.40) times more likely to have CAD than nonobese survivors ( P < 0.001). Conclusion CAD was present in over one third of survivors and was associated with lower exercise capacity. Obese survivors and those exposed to cyclophosphamide with high doses of vincristine and/or corticosteroids were at greatest risk.
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Christoffersen et al. (2020) conducted a cross-sectional in Adult survivors of childhood acute lymphoblastic leukemia (ALL) (n=663). Childhood acute lymphoblastic leukemia survivorship and treatment exposure (cyclophosphamide with vincristine >=38 mg/m2 and/or glucocorticoids >=10,000 mg/m2) vs. Matched community controls without a history of childhood cancer (or ALL survivors without high-intensity treatment exposure) was evaluated on Prevalence of cardiac autonomic dysfunction (CAD), defined as elevated resting heart rate (>=80 bpm) or abnormal heart rate recovery at 1-minute post-exercise (<=12 bpm with active cool down or <=18 bpm with passive seated recovery) (p=0.09). Adult survivors of childhood ALL had a 33.7% prevalence of cardiac autonomic dysfunction vs 27.6% in controls (p=0.09), with significantly lower heart rate recovery (22 vs 25 bpm, p<0.001).
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